Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

• Published in: European journal of cancer (1990) Vol. 82; pp. 237 - 246
• Main Authors: Gligorov, J, Ataseven, B, Verrill, M, De Laurentiis, M, Jung, K.H, Azim, H.A, Al-Sakaff, N, Lauer, S, Shing, M, Pivot, X
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2017; Elsevier Science Ltd
• Subjects: Adjuvant; Adjuvant therapy; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Cancer; Chemotherapy; Chemotherapy, Adjuvant; Congestive heart failure; Epidermal growth factor; ErbB-2 protein; Female; Heart; Hematology, Oncology and Palliative Medicine; HER2/neu; Herceptin; Humans; Hypodermic needles; Immunotherapy; Injections, Subcutaneous - adverse effects; Intravenous administration; Middle Aged; Monoclonal antibodies; Patients; Receptor, ErbB-2 - metabolism; Safety; Subcutaneous; Subgroups; Survival Analysis; Targeted cancer therapy; Therapy; Trastuzumab; Trastuzumab - administration & dosage; Trastuzumab - adverse effects; Young Adult; Herceptin; Adjuvant; Breast cancer; HER2/neu; Subcutaneous; Trastuzumab
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2017.05.010

Abstract Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.